The putative bacterial oxygen sensor Pseudomonas prolyl hydroxylase (PPHD) suppresses antibiotic resistance and pathogenicity in Pseudomonas aeruginosa.

Abstract

Pseudomonas aeruginosa is an extracellular opportunistic bacterial pathogen commonly associated with infectious complications in susceptible individuals, such as those with underlying diseases including HIV/AIDS and cystic fibrosis. Antibiotic resistance in multiple strains of P. aeruginosa is a rapidly developing clinical problem. We have previously demonstrated that the oxygen levels at the site of P. aeruginosa infection can strongly influence virulence and antibiotic resistance in this pathogen, although the oxygen-sensing and -signaling mechanisms underpinning this response have remained unknown. In this study, we investigated the potential role of the putative oxygen sensor Pseudomonas prolyl hydroxylase (PPHD) in the control of virulence and antibiotic resistance in P. aeruginosa We found that a P. aeruginosa strain lacking PPHD (PAO310) exhibits increased virulence associated with increased bacterial motility. Furthermore, PPHD-deficient P. aeruginosa displayed enhanced antibiotic resistance against tetracycline through increased expression of the xenobiotic transporters mexEF-oprN and MexXY. Of note, the effect of the PPHD knockout on antibiotic resistance was phenocopied in bacteria exposed to atmospheric hypoxia. We conclude that PPHD is a putative bacterial oxygen sensor that may link microenvironmental oxygen levels to virulence and antibiotic resistance in P. aeruginosa.

• Authors: Bettina Schaible, Bianca Crifo, Kirsten Schaffer, Cormac T Taylor
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 295 Issue 5 Pg. 1195-1201 (01 31 2020) ISSN: 1083-351X [Electronic] United States
• PMID: 31826919 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 Schaible et al.

Chemical References

• Bacterial Outer Membrane Proteins
• Bacterial Proteins
• MexXY protein, Pseudomonas aeruginosa
• OprN protein, Pseudomonas aeruginosa
• Prolyl Hydroxylases
• Tetracycline
• Oxygen

Topics

• Animals
• Bacterial Outer Membrane Proteins (metabolism)
• Bacterial Proteins (metabolism)
• Drug Resistance, Multiple, Bacterial (genetics)
• Hypoxia
• Larva (microbiology)
• Microbial Sensitivity Tests
• Moths (microbiology)
• Oxygen
• Prolyl Hydroxylases (genetics, metabolism)
• Pseudomonas aeruginosa (enzymology, genetics, metabolism, pathogenicity)
• Tetracycline (pharmacology)
• Virulence (drug effects, genetics)